Phenotyping and Classifying Asthma Exacerbations (ExCluSieF)

Phenotyping and Classifying of Childhood and Adult Asthma Exacerbations: Towards Personalised Treatment. An Observational Multicentre Study.

An observational study in patients between 12 and 70 years old with an acute asthma exacerbation, to determine the relation between phenotypical characteristics and the treatment response.

Study Overview

• Status: Active, not recruiting
• Conditions: Asthma Attack
• Intervention / Treatment: Behavioral: Questionnaires; Device: Spirometry; Device: Fractional Exhaled Nitric Oxide (FeNO); Device: Corsano watch; Device: e-Nose; Procedure: Blood sample; Procedure: Nasopharyngeal swabs and nasal lining fluid; Device: Sputum culture

Detailed Description

Rationale: Asthma is a heterogeneous inflammatory respiratory disease affecting 8 - 9% of the European population. Acute asthma exacerbation (AAE) is characterized as an acute worsening of symptoms and is treated inconsistently with steroids with or without antibiotics. In order to adjust and personalise exacerbation treatment, phenotyping and classifying of asthma exacerbations would be required. Therefore, we want to classify patients with AAEs phenotypically in relation to the treatment response.

Objective: The primary objective of the study is to determine the relationship between exacerbation treatment response at day 7 and the phenotypical characteristics of asthma exacerbations. Secondary objectives are 1) developing a prediction model based on biomarkers and/or clinical data to predict the treatment response of AAEs 2) comparing the environmental, inflammatory, microbiological and lipid parameters of patients diagnosed with asthma between exacerbation phase and recovery (baseline).

Study design: A prospective cohort multicentre study. Study population: Patients aged 12 - 70 years, diagnosed with mild to severe asthma according to the Global Initiative for Asthma (GINA) guidelines. Patients will be included at the onset of a severe asthma exacerbation.

Main study parameters/endpoints: Primary endpoint is the relation of phenotypical characteristics with treatment response at day 7, defined by 1) the physician - and patient rated global evaluation of treatment effectiveness (GETE) score 2) difference in Asthma Control Questionnaire 5 (ACQ-5) (> 0.5) 3) difference in handheld spirometry values like forced expiratory volume (FEV1 ≥ 10%). Treatment response will be classified as excellent, good, moderate or poor. Secondary endpoints are 1) a prediction model for the treatment response of AAE 2) aetiology of the AAE 3) blood and local respiratory parameters; microbiota composition; lipid metabolomics and volatile compounds composition at baseline and AAE.

• Study Type: Observational
• Enrollment (Estimated): 200

Contacts and Locations

Study Locations

• Netherlands
  • Rotterdam, Netherlands, 3045PM
    • Franciscus Gasthuis & Vlietland

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 70 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients aged 12 - 70 years, diagnosed with mild to severe asthma according to the Global Initiative for Asthma (GINA) guidelines. Patients will be included at the onset of a (severe) asthma exacerbation.

Description

Inclusion Criteria:

• Patient diagnosed with asthma according to the GINA guidelines between 12 and 70 years old. If patients are doctor's diagnosed with asthma based on clinical data, the further diagnostics will be performed to confirm the asthma diagnosis after the AAE.
• Mild to severe asthma, treated according to GINA guidelines with medium - or high dose inhaled corticosteroids (with or without LABA) or treated with a low dose inhaled corticosteroids combined LABA or leukotriene - receptor antagonist.
• Asthma exacerbation, indicated for systemic corticosteroids.
• Written personal and/or parental informed consent, prior to any study procedures.
• Eligibility and willingness to present during an asthma exacerbation at the Franciscus Gasthuis hospital.
• Ability to use e - health applications.

Exclusion Criteria:

• Immunosuppressive maintenance medication (azithromycin, systemic corticosteroids maintenance therapy and other) or recently (< 6 weeks) discontinued these medications. (Desensitization therapy indicated for allergies can be included in the study)
• Maintenance medication or recently discontinued (< 6 weeks) biologicals.
• Other underlying inflammatory or auto-immune diseases, such as rheumatologic disease.
• Involvement in the planning and/or conduct of the study (applies to both investigator staff and/or staff at the study site)
• Pregnancy, because of the possible altered immunological status.(31)
• Participation in an interventional study or randomised controlled trial.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Asthma exacerbation; Patients with an asthma exacerbation who are diagnosed with mild to severe asthma according to the GINA guidelines

Behavioral: Questionnaires; Questionnaires about asthma control and quality of life; Device: Spirometry; Spirometry monitoring at home; Device: Fractional Exhaled Nitric Oxide (FeNO); Measuring fractional exhaled nitric oxide at home; Device: Corsano watch; Monitoring vital parameters at home; Device: e-Nose; Breathprint will be performed using e-Nose; Procedure: Blood sample; Blood sample for standard care and 10 ml extra will be taken; Procedure: Nasopharyngeal swabs and nasal lining fluid; Nasopharyngeal swabs and nasal lining fluid will be performed; Device: Sputum culture; If patients produce sputum, the sputum will be analysed

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relation of phenotypical characteristics with treatment response	Relation of phenotyipcal characteristics with treatment response defined by 1) the physician - and patient rated global evaluation of treatment effectiveness (GETE) score 2) difference in Asthma Control Questionnaire 5 (ACQ-5) (> 0.5) 3) difference in handheld spirometry values like forced expiratory volume (FEV1 ≥ 10%).	7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prediction model for the treatment response of acute asthma exacerbation	Creating a prediction model for the treatment response of acute asthma exacerbation with phenotypical characteristics	42 days
Aetiology of the acute asthma exacerbation	Analysing the aetiology of the acute asthma exacerbations	42 days
Immune system and microbiome	Analysing the blood and local respiratory parameters; the microbiota composition; lipid metabolomics and volatile compounds composition at baseline and acute asthma exacerbation	42 days

Collaborators and Investigators

• Sponsor: Franciscus Gasthuis
• Collaborators: Erasmus Medical Center; TNO
• Investigators: Principal Investigator: Gert-Jan Braunstahl, MD, PhD, Franciscus Gasthuis & Vlietland; Principal Investigator: Gerdien Tramper, MD, PhD, Franciscus Gasthuis & Vlietland

Study record dates

Study Major Dates

• Study Start (Actual): September 28, 2022
• Primary Completion (Actual): March 31, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: March 22, 2022
• First Submitted That Met QC Criteria: March 22, 2022
• First Posted (Actual): March 31, 2022

Study Record Updates

• Last Update Posted (Actual): August 21, 2025
• Last Update Submitted That Met QC Criteria: August 20, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Treatment; Asthma; Exacerbation; Phenotyping; Classification
• Additional Relevant MeSH Terms: Immune System Diseases; Respiratory Tract Diseases; Lung Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Asthma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Neurotransmitter Agents; Antioxidants; Protective Agents; Respiratory System Agents; Free Radical Scavengers; Anti-Asthmatic Agents; Bronchodilator Agents; Vasodilator Agents; Endothelium-Dependent Relaxing Factors; Gasotransmitters; Nitric Oxide
• Other Study ID Numbers: NL79257.100.21

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No